Why does depression lower BDNF levels

New mode of action of antidepressants discovered

Scientists at the University Medical Center Freiburg, together with international colleagues, have discovered a new mechanism by which antidepressants work in the brain. They dock on nerve cells at a previously unknown location and thus unfold their mood-enhancing effect.

They bind to the receptor of the so-called brain derived neurotrophic factor (BDNF), which leads to improved activity in brain regions that are impaired in depressed patients.

Look for agents that bind to the BDNF receptor

The findings now enable the targeted search for active ingredients that bind to the BDNF receptor, according to a press release. The study was published in the journal Cell.

"With the BDNF receptor as a docking point, we can for the first time directly explain how antidepressants work and why it takes so long for them to work," explains Prof. Claus Normann, research group leader at the Clinic for Psychiatry and Psychotherapy at the Freiburg University Medical Center.

Easier perception of positive information

The improved brain activity was generated in the mouse experiment by different types of antidepressants such as selective serontonin reuptake inhibitors (SSRIs) or ketamine. It facilitates learning and the perception of positive information.

It was previously assumed that they act by increasing the messenger substance serotonin in the brain, but it remained unclear exactly how this works.

New mode of action of antidepressants discovered

"By stimulating the BDNF, the brain can better absorb new, positive information from the environment or during psychotherapy and recovers from its depressed state," says Normann. This intervenes in a central learning and adaptation mechanism called synaptic plasticity.

The researchers not only discovered the new mode of action of antidepressants, but also another important factor: "Interestingly, this binding site needs a normal cholesterol level in order to be optimally active." As the team showed, high or low cholesterol levels deform the BDNF receptor so that the active ingredients bind more poorly.

Photo: Adobe Stock / Pixel-Shot

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